The acute medical management of an upper GI bleed from peptic ulcer bleeding includes both hallmark and emerging medical therapies with which any Emergency Physician should be intimately familiar. Many of these therapies are adopted recommendations from our Gastroenterology colleagues who ultimately perform emergent/non-emergent endoscopy on these patients. To understand why Gastroenterologists think the way they do, here is a review of these specific therapies along with the evidence behind them.

Taken from "Management of Patients with Peptic Ulcer Bleeding," American College of Gastroenterology (ACG) Practice Guidelines. Am J Gastroenterol 2012; 107:345–360.

PROKINETIC THERAPY: Erythromycin 250 mg (or 3mg/kg) IV infusion, 30 minutes before endoscopy. Alternative: Metoclopramide.

• ACG: Why we do it: "Erythromycin as a prokinetic agent is considered to improve diagnostic yield and decrease the need for repeat endoscopy."
• Evidence: Three randomized trials showed significant improvement in their primary endpoint related to visualization of mucosa.
• Evidence: Meta-analysis of these three trials revealed a very modest but significant benefit (relative risk (RR) = 1.13, (1.02–1.26); number needed to treat (NNT) = 9) in diagnosis at first endoscopy. Erythromycin did not significantly reduce clinical outcomes such as blood transfusions, hospital stay, or surgery, but did decrease the proportion of patients undergoing a second endoscopy
• Evidence: A randomized comparison of erythromycin, NG tube, or erythromycin plus NG tube in 253 patients with UGIB revealed no significant differences in visualization, diagnosis at first endoscopy, second-look endoscopy, further bleeding, or transfusions.

PROTON PUMP INHIBITOR: Pantoprazole 80 mg IV loading dose, followed by 8 mg/hour for 72 hours.

• ACG: Why we do it: "PPI therapy may be considered to decrease the proportion of patients who have higher risk stigmata of hemorrhage at endoscopy and who receive endoscopic therapy. If endoscopy will be delayed or cannot be performed, intravenous PPI is recommended to reduce further bleeding"
• Evidence: A Cochrane meta-analysis of six randomized trials (N = 2 ,223) of pre-endoscopic PPI therapy found no significant differences between PPI and control in mortality, rebleeding, or surgery.
• Evidence: A second Cochrane meta-analysis of randomized trials of patients showed that PPI therapy was associated with reduced rebleeding and surgery, but not mortality. In situations of delayed endoscopy or unavailable endoscpy, PPI therapy may improve clinical outcomes.

NASOGASTRIC TUBE:

• ACG Recommendation: "NG or orogastric lavage is not required in patients with UGIB for diagnosis, prognosis, visualization, or therapeutic effect."
• Evidence behind "Documenting UGI Source": A clear or bile-stained NG aspirate may be seen in up to 18 % of patients with an upper GI
  source. In a different study, 15% of patients with a clear or bile-stained NG aspirate had active bleeding or non-bleeding visible vessel compared with 23% with coffee gounds and 45% with bloody aspirates. Further muddying the picture, physicians are incorrect about 50% of the time when they report bile in the aspirate.
• Evidence behind "Prognostic Value.": While it seems logical that a persistently bloody NG aspirate would be suggestive of more severe UGIB, this is inconsistently supported by literature. It has been reported that frank blood from NG aspirate is associated with severe UGIB (severe defined as requiring >5 units of PRBC transfusion). However, in a prospective trial of 325 patients, the patients who developed shock had a clear aspirate 11% of the time, coffee-grounds aspirate 36% of the time, and bloody aspirate 60% of the time.
• Evidence behing "Improvement of Visualization.": A small randomized comparison of a 40 French orogastric tube vs. no lavage in 38 patients showed a significantly higher proportion with excellent visualization in the fundus with a trend in the antrum. Howeve this size tube is large and uncomfortable for patients and the study gave sedation to patients which is not always achievable.
• Evidence behing "Therapeutic Effect.": There is an older belief that NG lavage with iced saline would stop bleeding ulcers however this has not been proven. Studies in dogs with experimentally induced ulcers indicated that results with lavage are no better and may even be worse at temperatures of 0–4 °C.

OTHER THERAPIES TO CONSIDER FOR PEPTIC ULCER UPPER GI BLEED

Taken from UpToDate: "Approach to acute upper gastrointestinal bleeding in adults." John R Saltzman, MD, FACP, FACG, FASGE, AGAF. 2015.

SOMATOSTATIN ANALOG: Octreotide IV 50 mcg bolus, followed by continuous IV infusion of 25 to 50 mcg/hour for 2 to 5 days. Can repeat bolus in the first hour if hemorrhage not controlled.

• "Somatostatin, or its analog octreotide is used in the treatment of variceal bleeding and may also reduce the risk of bleeding due to nonvariceal causes."
• "Octreotide is not recommended for routine use in patients with acute nonvariceal upper GI bleeding, but it can be used as adjunctive therapy in some cases. Its role is generally limited to settings in which endoscopy is unavailable or as a means to help stabilize patients before definitive therapy can be performed."

TRANEXAMIC ACID: Loading dose: IV 1000 mg over 10 minutes, followed by 1,000 mg over the next 8 hours. (Dose for trauma-associated hemorrhage. No agreed upon dose for UGIB)

• A meta-analysis that included eight randomized trials of tranexamic acid in patients with upper GI bleeding found a benefit with regard to mortality but not with regard to bleeding, surgery, or transfusion requirements.
• However when only studies that used antiulcer drugs and/or endoscopic therapy were included, there was no beneficial effect.

Don't forget reversal agents for coumadin and NOACs when appropriate!

References:

• Pateron D , Vicaut E , Debuc E et al. Erythromycin infusion or gastric lavage for upper gastrointestinal bleeding: a multicenter randomized controlled trial . Ann Emerg Med 2011 ; 57 : 582 – 9 .

• Sreedharan A , Martin J , Leontiadis GI et al. Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding . Cochrane Database Syst Rev 2010 (7): CD005415 .

• Lau JY , Leung WK , Wu JCY et al. Omeprazole before endoscopy in patients with gastrointestinal bleeding . N Engl J Med 2007 ; 356 : 1631 – 40

• Leontiadis GI , Sharma VK , Howden CW . Proton pump inhibitor therapy for peptic ulcer bleeding: Cochrane collaboration meta-analysis of randomized controlled trials . Mayo Clin Proc 2007 ; 82 : 286 – 96 .

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• Pateron D, Vicaut E, Debuc E, et al. Erythromycin infusion or gastric lavage for upper gastrointestinal bleeding: a multicenter randomized controlled trial. Ann Emerg Med 2011; 57:582.
• Imperiale TF, Birgisson S. Somatostatin or octreotide compared with H2 antagonists and placebo in the management of acute nonvariceal upper gastrointestinal hemorrhage: a meta-analysis. Ann Intern Med 1997; 127:1062.